Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1994 Feb 1;13(3):606–615. doi: 10.1002/j.1460-2075.1994.tb06298.x

A fission yeast RCC1-related protein is required for the mitosis to interphase transition.

S Sazer 1, P Nurse 1
PMCID: PMC394850  PMID: 8313905

Abstract

The isolation and characterization of the mutant dcdts (defect in chromatin decondensation) has led to the identification of two conserved proteins required for the re-establishment of the interphase state following the completion of mitosis. The gene that rescues the dcdts mutant encodes a protein similar to the human chromatin binding protein, RCC1. A suppressor of dcdts encodes a protein nearly identical to the human GTP-binding protein, RAN, encoded by the TC4 gene. These results indicate that completion of mitosis is regulated at least in part by a GTPase molecular switch. The gene and suppressor of dcdts are identical to the previously described Schizosaccharomyces pombe genes pim1 (premature initiation of mitosis) and spi1 (suppressor of pim), but the dcdts mutant does not enter mitosis prematurely, a phenotype that has been reported for the pim1-46ts mutant. Based on our studies we propose that the pim1 gene product is required for regulating chromatin condensation with a primary role at the end of mitosis and pleiotropic effects on other aspects of cell behavior.

Full text

PDF
606

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Axton J. M., Dombrádi V., Cohen P. T., Glover D. M. One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis. Cell. 1990 Oct 5;63(1):33–46. doi: 10.1016/0092-8674(90)90286-n. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  3. Barbet N., Muriel W. J., Carr A. M. Versatile shuttle vectors and genomic libraries for use with Schizosaccharomyces pombe. Gene. 1992 May 1;114(1):59–66. doi: 10.1016/0378-1119(92)90707-v. [DOI] [PubMed] [Google Scholar]
  4. Belhumeur P., Lee A., Tam R., DiPaolo T., Fortin N., Clark M. W. GSP1 and GSP2, genetic suppressors of the prp20-1 mutant in Saccharomyces cerevisiae: GTP-binding proteins involved in the maintenance of nuclear organization. Mol Cell Biol. 1993 Apr;13(4):2152–2161. doi: 10.1128/mcb.13.4.2152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bischoff F. R., Ponstingl H. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature. 1991 Nov 7;354(6348):80–82. doi: 10.1038/354080a0. [DOI] [PubMed] [Google Scholar]
  6. Bischoff F. R., Ponstingl H. Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10830–10834. doi: 10.1073/pnas.88.23.10830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Booher R., Beach D. Involvement of a type 1 protein phosphatase encoded by bws1+ in fission yeast mitotic control. Cell. 1989 Jun 16;57(6):1009–1016. doi: 10.1016/0092-8674(89)90339-5. [DOI] [PubMed] [Google Scholar]
  8. Bourne H. R., Sanders D. A., McCormick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature. 1990 Nov 8;348(6297):125–132. doi: 10.1038/348125a0. [DOI] [PubMed] [Google Scholar]
  9. Bourne H. R., Sanders D. A., McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature. 1991 Jan 10;349(6305):117–127. doi: 10.1038/349117a0. [DOI] [PubMed] [Google Scholar]
  10. Broek D., Toda T., Michaeli T., Levin L., Birchmeier C., Zoller M., Powers S., Wigler M. The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Cell. 1987 Mar 13;48(5):789–799. doi: 10.1016/0092-8674(87)90076-6. [DOI] [PubMed] [Google Scholar]
  11. Compton D. A., Cleveland D. W. NuMA is required for the proper completion of mitosis. J Cell Biol. 1993 Feb;120(4):947–957. doi: 10.1083/jcb.120.4.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dasso M., Nishitani H., Kornbluth S., Nishimoto T., Newport J. W. RCC1, a regulator of mitosis, is essential for DNA replication. Mol Cell Biol. 1992 Aug;12(8):3337–3345. doi: 10.1128/mcb.12.8.3337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dasso M. RCC1 in the cell cycle: the regulator of chromosome condensation takes on new roles. Trends Biochem Sci. 1993 Mar;18(3):96–101. doi: 10.1016/0968-0004(93)90161-f. [DOI] [PubMed] [Google Scholar]
  14. Doonan J. H., Morris N. R. The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1. Cell. 1989 Jun 16;57(6):987–996. doi: 10.1016/0092-8674(89)90337-1. [DOI] [PubMed] [Google Scholar]
  15. Drivas G. T., Shih A., Coutavas E., Rush M. G., D'Eustachio P. Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Mol Cell Biol. 1990 Apr;10(4):1793–1798. doi: 10.1128/mcb.10.4.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fantes P. Epistatic gene interactions in the control of division in fission yeast. Nature. 1979 May 31;279(5712):428–430. doi: 10.1038/279428a0. [DOI] [PubMed] [Google Scholar]
  17. Fernandez A., Brautigan D. L., Lamb N. J. Protein phosphatase type 1 in mammalian cell mitosis: chromosomal localization and involvement in mitotic exit. J Cell Biol. 1992 Mar;116(6):1421–1430. doi: 10.1083/jcb.116.6.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fikes J. D., Becker D. M., Winston F., Guarente L. Striking conservation of TFIID in Schizosaccharomyces pombe and Saccharomyces cerevisiae. Nature. 1990 Jul 19;346(6281):291–294. doi: 10.1038/346291a0. [DOI] [PubMed] [Google Scholar]
  19. Fleig U. N., Gould K. L., Nurse P. A dominant negative allele of p34cdc2 shows altered phosphoamino acid content and sequesters p56cdc13 cyclin. Mol Cell Biol. 1992 May;12(5):2295–2301. doi: 10.1128/mcb.12.5.2295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Frasch M. The maternally expressed Drosophila gene encoding the chromatin-binding protein BJ1 is a homolog of the vertebrate gene Regulator of Chromatin Condensation, RCC1. EMBO J. 1991 May;10(5):1225–1236. doi: 10.1002/j.1460-2075.1991.tb08064.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gould K. L., Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. doi: 10.1038/342039a0. [DOI] [PubMed] [Google Scholar]
  22. Hagan I. M., Hyams J. S. The use of cell division cycle mutants to investigate the control of microtubule distribution in the fission yeast Schizosaccharomyces pombe. J Cell Sci. 1988 Mar;89(Pt 3):343–357. doi: 10.1242/jcs.89.3.343. [DOI] [PubMed] [Google Scholar]
  23. Hagan I., Hayles J., Nurse P. Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis. J Cell Sci. 1988 Dec;91(Pt 4):587–595. doi: 10.1242/jcs.91.4.587. [DOI] [PubMed] [Google Scholar]
  24. Hoheisel J. D., Maier E., Mott R., McCarthy L., Grigoriev A. V., Schalkwyk L. C., Nizetic D., Francis F., Lehrach H. High resolution cosmid and P1 maps spanning the 14 Mb genome of the fission yeast S. pombe. Cell. 1993 Apr 9;73(1):109–120. doi: 10.1016/0092-8674(93)90164-l. [DOI] [PubMed] [Google Scholar]
  25. Holloway S. L., Glotzer M., King R. W., Murray A. W. Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell. 1993 Jul 2;73(7):1393–1402. doi: 10.1016/0092-8674(93)90364-v. [DOI] [PubMed] [Google Scholar]
  26. Maier E., Hoheisel J. D., McCarthy L., Mott R., Grigoriev A. V., Monaco A. P., Larin Z., Lehrach H. Complete coverage of the Schizosaccharomyces pombe genome in yeast artificial chromosomes. Nat Genet. 1992 Jul;1(4):273–277. doi: 10.1038/ng0792-273. [DOI] [PubMed] [Google Scholar]
  27. Matsumoto T., Beach D. Interaction of the pim1/spi1 mitotic checkpoint with a protein phosphatase. Mol Biol Cell. 1993 Mar;4(3):337–345. doi: 10.1091/mbc.4.3.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Matsumoto T., Beach D. Premature initiation of mitosis in yeast lacking RCC1 or an interacting GTPase. Cell. 1991 Jul 26;66(2):347–360. doi: 10.1016/0092-8674(91)90624-8. [DOI] [PubMed] [Google Scholar]
  29. Maundrell K. nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine. J Biol Chem. 1990 Jul 5;265(19):10857–10864. [PubMed] [Google Scholar]
  30. Moore M. S., Blobel G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature. 1993 Oct 14;365(6447):661–663. doi: 10.1038/365661a0. [DOI] [PubMed] [Google Scholar]
  31. Moreno S., Hayles J., Nurse P. Regulation of p34cdc2 protein kinase during mitosis. Cell. 1989 Jul 28;58(2):361–372. doi: 10.1016/0092-8674(89)90850-7. [DOI] [PubMed] [Google Scholar]
  32. Moreno S., Klar A., Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l. [DOI] [PubMed] [Google Scholar]
  33. Murray A. W., Solomon M. J., Kirschner M. W. The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. Nature. 1989 May 25;339(6222):280–286. doi: 10.1038/339280a0. [DOI] [PubMed] [Google Scholar]
  34. Nasmyth K., Nurse P. Cell division cycle mutants altered in DNA replication and mitosis in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet. 1981;182(1):119–124. doi: 10.1007/BF00422777. [DOI] [PubMed] [Google Scholar]
  35. Nishimoto T., Eilen E., Basilico C. Premature of chromosome condensation in a ts DNA- mutant of BHK cells. Cell. 1978 Oct;15(2):475–483. doi: 10.1016/0092-8674(78)90017-x. [DOI] [PubMed] [Google Scholar]
  36. Nishitani H., Ohtsubo M., Yamashita K., Iida H., Pines J., Yasudo H., Shibata Y., Hunter T., Nishimoto T. Loss of RCC1, a nuclear DNA-binding protein, uncouples the completion of DNA replication from the activation of cdc2 protein kinase and mitosis. EMBO J. 1991 Jun;10(6):1555–1564. doi: 10.1002/j.1460-2075.1991.tb07675.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nurse P. Genetic control of cell size at cell division in yeast. Nature. 1975 Aug 14;256(5518):547–551. doi: 10.1038/256547a0. [DOI] [PubMed] [Google Scholar]
  38. Nurse P., Thuriaux P., Nasmyth K. Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet. 1976 Jul 23;146(2):167–178. doi: 10.1007/BF00268085. [DOI] [PubMed] [Google Scholar]
  39. Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. doi: 10.1038/344503a0. [DOI] [PubMed] [Google Scholar]
  40. Ohkura H., Kinoshita N., Miyatani S., Toda T., Yanagida M. The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases. Cell. 1989 Jun 16;57(6):997–1007. doi: 10.1016/0092-8674(89)90338-3. [DOI] [PubMed] [Google Scholar]
  41. Pfeffer S. R. GTP-binding proteins in intracellular transport. Trends Cell Biol. 1992 Feb;2(2):41–46. doi: 10.1016/0962-8924(92)90161-f. [DOI] [PubMed] [Google Scholar]
  42. Poccia D. Remodeling of nucleoproteins during gametogenesis, fertilization, and early development. Int Rev Cytol. 1986;105:1–65. doi: 10.1016/s0074-7696(08)61061-x. [DOI] [PubMed] [Google Scholar]
  43. Ren M., Drivas G., D'Eustachio P., Rush M. G. Ran/TC4: a small nuclear GTP-binding protein that regulates DNA synthesis. J Cell Biol. 1993 Jan;120(2):313–323. doi: 10.1083/jcb.120.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Robinson L. C., Gibbs J. B., Marshall M. S., Sigal I. S., Tatchell K. CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae. Science. 1987 Mar 6;235(4793):1218–1221. doi: 10.1126/science.3547648. [DOI] [PubMed] [Google Scholar]
  45. Sazer S., Sherwood S. W. Mitochondrial growth and DNA synthesis occur in the absence of nuclear DNA replication in fission yeast. J Cell Sci. 1990 Nov;97(Pt 3):509–516. doi: 10.1242/jcs.97.3.509. [DOI] [PubMed] [Google Scholar]
  46. Shimanuki M., Kinoshita N., Ohkura H., Yoshida T., Toda T., Yanagida M. Isolation and characterization of the fission yeast protein phosphatase gene ppe1+ involved in cell shape control and mitosis. Mol Biol Cell. 1993 Mar;4(3):303–313. doi: 10.1091/mbc.4.3.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Woods A., Sherwin T., Sasse R., MacRae T. H., Baines A. J., Gull K. Definition of individual components within the cytoskeleton of Trypanosoma brucei by a library of monoclonal antibodies. J Cell Sci. 1989 Jul;93(Pt 3):491–500. doi: 10.1242/jcs.93.3.491. [DOI] [PubMed] [Google Scholar]
  48. Yanagida M. Gene products required for chromosome separation. J Cell Sci Suppl. 1989;12:213–229. doi: 10.1242/jcs.1989.supplement_12.18. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES